title: Alterations of the enteric smooth musculature in diverticular disease.
abstract: BACKGROUND
  The pathogenesis of diverticular disease (DD) is considered to be multifactorial and involves intestinal motor disturbances and an underlying enteric neuromuscular pathology. While an enteric neuropathy has been well documented, actual studies on concomitant alterations of the enteric musculature are limited. This study is aimed at reassessing the smooth muscle tissue by histological, ultrastructural and molecular-biological approaches.
  
  
  METHODS
  Full-thickness sigmoid specimens were obtained from patients with DD (n = 20) and controls (n = 19). Morphometric analysis was performed to evaluate the thickness and connective tissue index of the circular and longitudinal muscle layers as well as the myenteric plexus. Structural alterations were determined by light and transmission electron microscopy. mRNA profiles of components of the contractile smooth muscle apparatus including smooth muscle α-actin, smoothelin, histone deacetylase 8, and smooth muscle myosin heavy chain (SMMHC) were assessed by qPCR. Altered gene expression levels were confirmed at protein level by immunohistochemistry.
  
  
  RESULTS
  Compared to controls, patients with DD showed (1) increased thickness of the circular and longitudinal muscle layers, (2) architectural alterations of smooth muscle cells, (3) increased connective tissue index of the longitudinal muscle layer, (4) focally reduced density of myofilaments at ultrastructural level, (5) specific down-regulation of SMMHC mRNA levels, (6) decreased immunoreactivity of SMMHC, (7) oligo-neuronal hypoganglionosis.
  
  
  CONCLUSIONS
  DD is associated with distinct structural and functional alterations of the enteric musculature. The enteric myopathy is characterized by disturbed muscular architecture, connective tissue replacement and loss of specific myofilaments and thus may contribute to the pathogenesis and progression of DD.
authors.affiliation: Department of Anatomy, Christian-Albrecht's University in Kiel, Otto-Hahn-Platz 8, 24118, Kiel, Germany, i.hellwig@anat.uni-kiel.de.
authors.forename: Ines
authors.initials: I
authors.lastname: Hellwig
authors.forename: Martina
authors.initials: M
authors.lastname: Böttner
authors.forename: Martina
authors.initials: M
authors.lastname: Barrenschee
authors.forename: Jonas
authors.initials: J
authors.lastname: Harde
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Egberts
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Thilo
authors.initials: T
authors.lastname: Wedel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004239:Diverticulitis, Colonic / Q000235:genetics / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009130:Muscle, Smooth / Q000166:cytology / Q000473:pathology*; D009197:Myenteric Plexus / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D012810:Sigmoid Diseases / Q000235:genetics / Q000473:pathology*
chemical_list: D012333:RNA, Messenger; D018995:Myosin Heavy Chains